Sustained release microspheres of metoclopramide using poly(D,L-lactide-co-glycolide) copolymers

Abstract

Metoclopramide was encapsulated with poly(D,L-lactide co glycolide) copolymers of different molecular weights using the emulsification/solvent evaporation technique. These polymers included poly(D,L-lactide-co-glycolide) 50:50 with inherent viscosity (i.v.) 0.2, and average molecular weight 8000, poly(D,Llactide-co-glycolide) 50:50 with i.v. 0.8 and average molecular weight 98000 and poly(D,L-lactide-co-glycolide) 85:15 with i.v. 1.4 and average molecular weight 220000. The effect of the polymers' molecular weights as well as the polymer-to-drug ratios on the yield, the particle size distribution, and the drug content of the microspheres was investigated. The release rate of the drug was studied for 96h in a phosphate buffer of pH7.4. The study also investigated the effect of the new poly(lactide-co-glycolide)-H series on the characteristics of the prepared microspheres. Data revealed that a higher yield was obtained with polymers of lower molecular weights. A lower yield was also obtained with increasing the drug-to-polymer ratios for all the investigated polymers. The drug content of the microspheres was lower than expected, ranging from 49-85%, which suggested a chemical interaction between the drug and the polymers, as proved by differential scanning calorimetry (DSC) and infra red (IR) studies. A higher interaction was obtained with the H-series of the copolymers. The release of the drug mainly followed zero order kinetics on increasing either the polymers' molecular weights or the polymer-to-drug ratios. Diffusion kinetics was observed only with those batches prepared with low polymer-to-drug ratios. The release rate was a function of both the polymers' molecular weights and the drug-to-polymer ratios.

Keywords::

• Metoclopramide Microspheres Sustained Release Poly Lactide-COGLYCOLIDE